• DNA double strand break
• Gamma-H2AX (γ-H2AX)
• preoperative concurrent chemoradiation
• rectal cancer
• tumor regression grade (TRG)

• Neoadjuvant chemoradiotherapy
• Neoplasm
• Neuroendocrine carcinomas
• PDNEC

• Humans
• Anal Canal
• Rectum
• Pelvis
• Chemoradiotherapy
• Neuroendocrine Tumors
• Carcinoma, Neuroendocrine/therapy

• Aarhus University Hospital

• pathological response rate
• rectal cancer
• survival
• three-dimensional conformal radiotherapy
• toxicity

• Chemotherapy
• Colorectal cancer
• Immunotherapy
• Oncolytic viral therapy
• Probiotics
• RNA interference

• DNA damage
• GW4869
• MicroRNA
• apoptosis
• exosome
• radiation-induced intestinal injury
• total body irradiation

• Animals
• Apoptosis/physiology
• Cell Proliferation/physiology
• DNA Damage/physiology
• Exosomes/metabolism
• Gamma Rays
• Intestinal Diseases/metabolism
• Intestinal Diseases/pathology
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/pathology
• Intestine, Small/metabolism
• Intestine, Small/pathology
• Male
• Mice, Inbred BALB C
• MicroRNAs/metabolism
• NF-E2-Related Factor 2/metabolism
• Radiation Injuries, Experimental
• Whole-Body Irradiation
• Mice

• IMRT
• preoperative radiotherapy
• rectal cancer
• surgery
• three-dimensional conformal radiotherapy

• National Natural Science Foundation of China

Helical tomotherapy (HT) has been recently introduced in the neoadjuvant treatment of locally advanced rectal cancer. Aim of this study is to report the toxicity and local control rates of a large series of locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and HT under daily image guidance followed by surgery.

Data from 117 locally advanced rectal cancer patients treated at two Swiss Radiotherapy departments were collected and analyzed. Radiotherapy consisted of 45 Gy (1.8 Gy/fraction, 5 fractions/week delivered in 5 weeks) to the regional pelvic lymph nodes. Seventy patients also received a simultaneous integrated boost (SIB) up to 50 Gy to the tumor and involved nodes (2 Gy/fraction, 5 fractions/week delivered in 5 weeks). Chemotherapy consisted of capecitabine 825 mg/m², twice daily, during the irradiation days. After a median interval of 59 days [95% confidence interval (CI) 53–65 days), all patients underwent surgery.

Median follow-up was 45 months (range 4–90 months). The overall rate of acute grade 2–4 toxicity was 18.8% (n = 22). Four patients (3.4%) presented a grade 3 dermatitis (n = 1) or diarrhea (n = 3), and 1 (0.8%) demonstrated grade 4 rectal toxicity. No patients presented with grade ≥ 3 hematologic toxicity. Six patients (5.1%) had late grade 3 gastrointestinal toxicity. The 4-year local control rate was 88.4% (95% CI 87.5–88.5%).

Neoadjuvant chemoradiotherapy delivered with HT under daily image guidance is well tolerated and shows a high 4-year local control rates.

• Helical tomotherapy
• Image-guided radiotherapy
• Neoadjuvant chemoradiotherapy
• Rectal cancer
• Toxicity

• Radiation
• intensity modulated radiotherapy (IMRT)
• rectal cancer

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint.

All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted.

Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR.

IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

• IMRT
• chemoradiation
• neoadjuvant
• rectal cancer
• response

In colorectal cancer, immune effectors may be determinative for disease outcome. Following curatively intended combined-modality therapy in locally advanced rectal cancer metastatic disease still remains a dominant cause of failure. Here, we investigated whether circulating immune factors might correlate with outcome. An antibody array was applied to assay changes of approximately 500 proteins in serial serum samples collected from patients during oxaliplatin-containing induction chemotherapy and sequential chemoradiotherapy before final pelvic surgery. Array data was analyzed by the Significance Analysis of Microarrays software and indicated significant alterations in serum osteoprotegerin (TNFRSF11B) during the treatment course, which were confirmed by osteoprotegerin measures using a single-parameter immunoassay. Patients experiencing increase in circulating osteoprotegerin during the chemotherapy had significantly better 5-year progression-free survival than those without increase (78% versus 48%; P = 0.009 by log-rank test). Hence, systemic release of this soluble tumor necrosis factor decoy receptor following the induction phase of neoadjuvant therapy was associated with favorable long-term outcome in patients given curatively intended chemoradiotherapy and surgery but with metastatic disease as the main adverse event. This finding suggests that osteoprotegerin may mediate or reflect systemic anti-tumor immunity invoked by combined-modality therapy in locally advanced rectal cancer.

• metastasis
• osteoprotegerin
• oxaliplatin
• radiotherapy
• rectal cancer

Intensity modulated radiation therapy (IMRT) has been rapidly incorporated into clinical practice because of its technological advantages over 3-dimensional conformal radiation therapy (CRT). We characterized trends in IMRT utilization in trimodality treatment of locally advanced rectal cancer at National Comprehensive Cancer Network cancer centers between 2005 and 2011.

Using the prospective National Comprehensive Cancer Network Colorectal Cancer Database, we determined treatment patterns for 976 patients with stage II-III rectal cancer who received pelvic radiation therapy at contributing centers between 2005 and 2011. Multivariable logistic regression was used to identify factors associated with IMRT versus 3-dimensional CRT. Radiation therapy compliance and time to completion were used to compare acute toxicity.

A total of 947 patients (97%) received 3-dimensional CRT (80%) or IMRT (17%). Ninety-eight percent of these patients received radiation therapy preoperatively, and 81% underwent definitive resection. IMRT use increased from <13% pre-2009 to >30% in 2010 and thereafter, with significant variability among institutions (range, 0%-43%). Other factors associated with IMRT use included age ≥65 years, dose >50.4 Gy, African-American race, and no transabdominal surgery. Rates of and time to radiation therapy completion were similar between the groups.

Although most patients with stage II-III rectal cancer at queried National Cancer Institute–designated cancer centers between 2005 and 2011 received 3-dimensional CRT, significant and increasing numbers received IMRT. IMRT utilization is highly variable among institutions and not uniform among sociodemographic groups but may be more consistently embraced in specific clinical settings. Given this trend, comparative-effectiveness research is needed to evaluate the benefits of IMRT for rectal cancer.

• Hematologic toxicity (HT)
• bone marrow
• chemoradiation
• colon cancer
• rectal cancer

Pathologic complete response to neoadjuvant chemoradiation therapy (CRT) is associated with improved outcomes for patients with locally advanced rectal cancer (LARC). Increased response rates have been reported with higher radiation doses, but these studies often lack long-term outcome and/or toxicity data. We conducted a case-control analysis of patients with LARC who underwent definitive CRT to determine the efficacy and safety of intensified treatment with a concomitant boost (CB) approach.

From 1995 to 2003, a phase 2 protocol examined CRT with 5-fluorouracil and CB radiation therapy (52.5 Gy in 5 weeks) for patients with LARC. Seventy-six protocol patients were matched (case-control approach) for surgery type, tumor (T) stage, and clinical nodal (N) stage with patients who received standard dose (SD) CRT (5-fluorouracil, 45 Gy). A chart review was performed. McNemar's test and Kaplan-Meier analyses were used for statistical analysis.

The SD and CB groups did not differ in tumor circumferential involvement and length, but the tumors of CB patients were closer to the anal verge (4.7 vs 5.7 cm; P = .02). Although tumor downstaging was higher in the CB cohort (76% vs 51%; P < .01), pathologic complete response rates did not differ (CB, 17.1% vs SD, 15.8%, P = 1.00). The incidence of grade ≥3 radiation-related toxicities was low and similar in both groups (CB, 10% vs SD, 3%, P = .22). Postoperative (anastomotic leak, wound complications/abscess, bleeding) and late (small bowel obstruction, stricture) complication rates did not differ between the groups (P > .05). The median follow-up was 11.9 years. The 5-year local control rates were higher for CB (100.0%) compared with SD (90.0%) patients (P = .01). CB patients had higher rates of 10-year progression-free survival (71.9% vs 57.6%, P < .01) and overall survival (71.6% vs 62.4%, P = .01) compared with SD patients.

CRT dose escalation for patients with LARC is safe and effective. The improved T-downstaging and local control observed in CB patients should encourage further dose escalation studies.

• IMRT
• SBRT
• novel technologies
• proton therapy
• rectal cancer

• chemoradiotherapy
• conformal
• image guidance
• locally advanced rectal cancer
• tomotherapy
• toxicity

• Adult
• Aged
• Aged, 80 and over
• Demography
• Factor Analysis, Statistical
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Pelvis/radiation effects
• Postoperative Complications/etiology
• Preoperative Care
• Prognosis
• Radiotherapy, Image-Guided/adverse effects
• Radiotherapy, Intensity-Modulated/adverse effects
• Rectal Neoplasms/pathology
• Rectal Neoplasms/radiotherapy
• Rectal Neoplasms/surgery
• Survival Analysis
• Treatment Outcome

• rectal cancer
• chemoradiotherapy
• 3d conformal radiotherapy
• volumetric modulated arc therapy
• tumor regression grading
• acute toxicity
• late toxicity

• Adult
• Aged
• Aged, 80 and over
• Combined Modality Therapy
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Staging
• Preoperative Care
• Radiotherapy, Conformal/adverse effects
• Radiotherapy, Conformal/methods
• Radiotherapy, Intensity-Modulated/adverse effects
• Radiotherapy, Intensity-Modulated/methods
• Rectal Neoplasms/mortality
• Rectal Neoplasms/pathology
• Rectal Neoplasms/radiotherapy
• Rectal Neoplasms/surgery
• Retrospective Studies
• Treatment Outcome

The study aims to assess the tolerance of elderly patients (70 years or older) with locally advanced rectal cancers to image-guided radiotherapy (IGRT). A retrospective review of 13 elderly patients with locally advanced rectal cancer who underwent preoperative chemoradiation using IGRT was performed. Grade 3–4 acute toxicities, survival, and long-term complications were compared to 17 younger patients (<70 years) with the same disease stage.

Grade 3–4 hematologic toxicities occurred in 7.6% and 0% (p = 0.4) and gastrointestinal toxicities, and, in 15.2% and 5% (p = 0.5), of elderly and younger patients, respectively. Surgery was aborted in three patients, two in the elderly group and one in the younger group. One patient in the elderly group died after surgery from cardiac arrhythmia. After a median follow-up of 34 months, five patients had died, two in the elderly and three in the younger group. The 3-year survival was 90.9% and 87.5% (p = 0.7) for the elderly and younger group respectively. Two patients in the younger group developed ischemic colitis and fecal incontinence. There was no statistically significant difference in acute and late toxicities as well as survival between the two groups.

Elderly patients with locally advanced rectal cancers may tolerate preoperative chemoradiation with IGRT as well as younger patients. Further prospective studies should be performed to investigate the potential of IGRT for possible cure in elderly patients with locally advanced rectal cancer.

• Evidence-Based Medicine
• Germany/epidemiology
• Humans
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/prevention & control
• Prevalence
• Rectal Neoplasms/mortality
• Rectal Neoplasms/therapy
• Risk Factors
• Survival Analysis
• Survival Rate